The enzyme superoxide dismutase (SOD) scavenges the superoxide radical (O2-) and thus acts as the major defense against the cytotoxic effects resulting from the univalent reduction of oxygen. The O2- radical, either by its direct action or by radicals generated by it, has been implicated in tissue damage resulting from senescence, inflammation, and radiation therapy. In ocular tissues at least six proteins with SOD activity have been identified. We propose to characterize the proteins of the cornea and lens which have SOD activity and to study their involvement in disorders of these tissues associated with aging, drug toxicity, and inflammation. Drugs can effect the SOD system in two ways: by inhibiting the SOD directly or by generating the superoxide radical. We propose to determine if drugs which are in common clinical use and which cause ocular disorders of the cornea and lens (e.g. cataract, black cornea) effect the SOD systems of these tissues. SOD is proposed to protect tissue during the inflammatory processes and has been used successfully in the treatment of some inflammatory conditions. We propose to investigate the effect of the superoxide radical, as generated by activated polymorphonuclear leukocytes, on the lens and corneal cells in culture as a model for inflammation: with age, enzyme activity can be decreased by either a reduced level of the enzyme or a modification of the enzyme which alters its activity. We propose to determine if the SOD activity of the cornea and lens decrease with age. Preliminary results indicated a decrease in the lens capsular enzyme which has important implications in the mechanism of senile cataract formation. We propose to investigate this enzyme in detail to determine if a structural modification has occurred and to examine the other SOD enzymes of cornea and lens for such a decrease. This research will determine if superoxide dismutase is involved in protection against, and hence possible control of, the ocular disorders of the lens and cornea caused by aging, inflammation and drug toxicity.